The objective of the proposed research is to systematically study factors involved in the pathogenesis, course, complications, prevention and treatment of bacterial endocarditis in an experimental rabbit model. The bacteria to be studied are: strains of Streptococcus viridans differing in extracellular polysaccharide production, strains of Staphylococcus aureus, Staphylococcus epidermidis, and Enterococci varying in antibiotic sensitivities, species of Enterobacteriaceae, species of anaerobic organisms with a range of oxygen tolerance, and stable L-Forms. The effect of host immunity on the number of organisms constituting a critical infecting dose will be determined. The clinical significance of a few persisting viable organisms in endocardial vegetations following antimicrobial therapy and the factors permitting their survival will be established. The effect of: the presence of a prosthetic device, a delay in instituting therapy, previous bacteriostatic antibiotic therapy, and anticoagulant or fibrinolytic therapy on the response of bacterial infections to several chemoprophylactic and therapeutic regimes will be investigated. Effective chemoprophylactic programs and optimal therapy will be established for strains of Staphylococcus aureus, Staphylococcus epidermidis, and Enterococci. The method to be employed involves the production of sterile vegetations on the endocardium of rabbits by the introduction of a sterile polyethylene catheter. These vegetations can then be colonized by test organisms administered by intravenous injection. Major emphasis will be placed on the evaluation of antimicrobial chemoprophylactic and therapeutic regimes that may be applicable to prevention and management of human bacterial endocarditis.